The occurrence of dramatic changes in mood, behavior, cognition and somatic functioning in some women in relation to the menstrual cycle has recently been the focus of a great deal of public scrutiny. This project is designed to study the psychobiology and treatment response of women with well defined menstrually-related mood disorders. The longitudinal screening methods developed by this group are capable of distinguishing women with menstrually-related mood syndromes from those who only believe that they have such a syndrome. We are continuing to attempt to identify potential psychobiological correlates of menstrually-related mood changes by assaying serial blood samples for relevant hormones and by performing neuroendocrine, cognitive and electrophysiological tests during the symptom-free and symptomatic phases of the menstrual cycle. At present, no basal, diagnostic group or menstrual cycle phase-related abnormalities of anterior pituitary (gonadotropins, prolactin) ovarian (estradiol, progesterone) or adrenal (cortisol) hormones have been detected. An excess of women with menstrually-related mood disorders compared with controls did, however, show a TSH response to TRH outside the normal range. We are additionally performing double-blind controlled studies of several putative therapeutic agents, including progesterone and pyridoxine. Evidence to date suggests no superior benefit of progesterone or medroxy-progesterone compared with placebo. The goals of this project are to detect and accurately describe menstrually-related mood disorders, explore their pathophysiology and response to pharmacological and environmental manipulation, and to document the relationship between reproductive endocrine change and disorders of mood as a way of further investigating the neurobiology of psychiatric illness.